Technical Field
The present disclosure relates to pharmaceuticals, compositions, drug-device combination products, and methods for treating medical conditions. In embodiments, compositions of the present disclosure may be used to treat chronic postoperative pain. In embodiments, the present disclosure relates to optimized pain management as a function of dosage and release kinetics of local anesthetics from implantable biodegradable microspheres.
Background of Related Art
Postoperative pain lasting for more than several days and even weeks affects many patients. For example, chronic pain following thoracotomy occurs at rest, e.g., with shallow breathing, and also has a pronounced movement-related component during coughing, stretching or twisting, e.g., mechano-hyperalgesia. While a variety of local and other anesthetic methods have been shown to reduce postoperative pain, the mechanisms of effect in chronic pain, unlike acute pain, are not well-understood since such drugs are known to act on multiple different targets.
Local anesthetics have previously been used perioperatively to reduce acute pain. Although peripheral nerve blocks, epidurals, and spinal anesthetics usually produce numbness for about 4 to about 12 hours, they are ineffective for long duration. Several other treatment strategies have also been employed, including continuous infusion of local anesthetics, e.g., through a catheter placed in the wound, and a variety of materials that slowly release drug(s) into tissue around the wound. Suitable delivery materials include multi-vesicular lipid suspensions, (e.g., EXPAREL®, a liposomal sustained-release bupivacaine formulation from Pacira Pharmaceuticals, Inc., San Diego, Calif.), bone waxes, biodegradable polymers, e.g., poly(lactic-co-glycolic acid) (“PLGA”) and other materials. Microspheres formed from biodegradable materials containing local anesthetic compositions are also known and have been used to treat acute postoperative pain (e.g., PLGA, such as those from Purdue Pharmaceuticals originally developed out of the Langer-Berde collaboration between MIT and Boston Children's Hospital). However, there is no information, data, or opinion in the public domain that would suggest any impact on chronic pain from these sustained-release formulations of bupivacaine.
There has been a lack of published information regarding the optimization of drug dosing and drug release kinetics of local anesthetics in treating chronic postoperative pain. Improved drug delivery compositions, including those suitable for treating chronic pain, remain desirable.